Birch Reduction of Arenes as an Easy Entry to γ-Spirolactones

A convenient method for the synthesis of gamma-spirolactones in only 2-3 steps is described. Birch reduction of inexpensive and commercially available aromatic carboxylic acids in the presence of ethylene oxide affords hydroxy acids, which undergo direct lactonization during work-up. Suitable precursors are methyl-substituted benzoic acids, naphthoic, and dicarboxylic acids. Subsequent hydrogenation proceeds smoothly with Pd/C as catalyst and saturated gamma-spirolactones are isolated in excellent yields and stereoselectivities. Thus, up to 3 new stereogenic centers can be constructed as sole diastereomers from achiral benzoic acids. Furthermore, it is possible to control the degree of saturation with Raney nickel or Wilkinson's catalyst to obtain products with 1 double bond. Overall, more than 30 new gamma-spirolactones have been synthesized in analytically pure form.

Automated summary

A convenient method for the synthesis of gamma-spirolactones in only 2-3 steps has been described, resulting in more than 30 new compounds. The process involves Birch reduction of aromatic carboxylic acids followed by direct lactonization, and subsequent hydrogenation with Pd/C catalyst. The method allows for the construction of up to 3 new stereogenic centers from achiral benzoic acids.